Two hypotheses pertain to the pathogenesis of the Sudden Infant Death Syndrome (SIDS): I. Our own physiologic studies have led us to hypothesize that infants with aborted sudden infant death syndrome have increased sympathoadrenal activity. II. Morphologic studies of the pulmonar vasculature by others have suggested that hypoxia plays an important role. In this proposal we will 1) investigate the role of maturation and sleep state on the ventilatory and cardiac responses to two levels of hypoxia in growing puppies and 2) study the role of endogenous catecholamines in the mediation of the ventilatory and cardiac responses to hypoxia in both REM and quiet sleep. Ventilation and ventilatory patterns will be measured using the barometric method. Sleep will be staged using the electroencephalogram, electro-oculogram and behavioral criteria. Heart rate and heart variability will be measured using a preprocessor of our own design and the QT index will be measured with a digitizer system. Arterial blood pressure and blood gases and oxygen consumption will also be measured. The role of endogenous catecholamines in mediating the response to hypoxia during sleep will be investigated by a) measuring circulating dopamine, norepinephrine, and epinephrine using radioenzymatic methods and relating them to physiologic changes and b) using selective alpha and beta blocking agents. Because preliminary studies in puppies have demonstrated sleep state related change in ventilation and heart rate with maturation, we plan to make serial studies during sleep in the first 6 weeks of life to determine whether there is a vulnerable period in the development of the puppy during which there is circulatory or ventilatory failure in response to hypoxia. We believe that these serial studies of responses to hypoxia during sleep in early life and the role of catecholamines in mediating these responses is an essential step in further understanding the pathogenesis of the Sudden Infant Death Syndrome and may also have biological and clinical implications for cardiac and ventilatory control in other age groups.